Treatment of H3-arachidonic acid (H3-C2O:4)-labeled, antibody-sensitized mouse resident peritoneal macrophages with rabbit serum complement (C), or C6-deficient rabbit serum (C6D RS)+C6 caused hydrolytic release of incorporated H3-C20:4 from phospholipids. High performance liquid chromatography revealed that the major radiolabeled products were C20:4, 6-keto-prostaglandin F1 alpha (6-k-PGF1 alpha) and prostaglandin E2. The time-course of production of 6-k-PGF1 alpha, measured by radioimmunoassay (RIA), was biphasic. The dose response curve of production of 6-K-PGF1 alpha with respect to C rose to a peak at a dose producing 60% cell lysis. C6D RS produced only small quantities of this metabolite but reconstitution with purified C6 increased release substantially. Thus, C5b-9 may play a significant role in generation of C20:4 and its metabolites. L. major is an intracellular parasite of macrophages in mammalian hosts in which the amastigote form is destroyed with less than 1% normal human serum. Its killing is mediated by the alternate complement pathway in which the lethal process is initiated within 30 sec of exposure to serum. Using human sera genetically deficient in terminal complement components we investigated the requirement for C5 through C9 in the cytolytic process. We found that the degree of cytotoxicity was related to both serum concentration and to the point at which the deficiency occurred and indicate that an incomplete membrane attack complex may mediate cytotoxicity for this parasite. Human peripheral blood monocytes (PBM) ingest and kill Asperigillus fumigatus (AF) conidia and Cryptococcus neoformans (CN) by a C3b dependent opsonization in normal human serum (NHS). Cultures of AF produce a metabolite (IO) that inhibits opsonization and killing of CN by preventing deposition of C3b to their surface. Experiments using both I125-anti C3b or I125-C3 demonstrated decreases of up to 80% C3b binding using 10% AF IO. IO had little direct effect on C3 or C4 levels and only C3 and not C4 levels were depressed (70%) from supernatants obtained from mixtures of opsonized CN.